SCEL

protein-coding

sciellin, the group of LIM domain containing

Gene summary

The protein encoded by this gene is a precursor to the cornified envelope of terminally differentiated keratinocytes. This protein localizes to the periphery of cells and may function in the assembly or regulation of proteins in the cornified envelope. Transcript variants encoding different isoforms exist. A transcript variant utilizing an alternative polyA signal has been described in the literature, but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_144777.3

Inheritance

—

ClinVar variants

P:1U:119B:4

Top phenotype

Moyamoya angiopathy

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr13:77,535,674-77,645,263

External References & Databases

Ensembl (ENSG00000136155)

Transcript & Mutation Effects

hg38 • Region Span ~109.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SCEL variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 104

Moyamoya angiopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144777.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense		1 clinvar	108 clinvar	4 clinvar		113
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	1	119	4	0	124

Highest pathogenic variant AF is 0.000011155292

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 244 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144777.3	RefSeq	NP_659001.2	32	MANE Select
ENST00000349847.4	Ensembl	ENSP00000302579.5	32	MANE Select
NM_001160706.2	RefSeq	NP_001154178.1	30	Standard
NM_003843.4	RefSeq	NP_003834.3	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

epidermis development
response to mechanical stimulus
embryo development ending in birth or egg hatching
keratinocyte differentiation
positive regulation of canonical Wnt signaling pathway

Molecular Function

protein binding
metal ion binding

Cellular Component

cornified envelope
cytoplasm
perinuclear region of cytoplasm
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000349847
Coding exons: 32
Length: 109590
Individuals with no LoFs: 125475
Homozygous LoFs: 1
Heterozygous LoFs: 272
Defined: 125748
p: 0.00109

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.286	332	347	0.957	0.0000167	4592
Missense (PolyPhen)		89	100.79	0.88305		1434
Synonymous	1.46	93	113	0.825	0.00000570	1165
Loss of Function	1.50	38	49.4	0.769	0.00000234	623

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0099	0.0099	notable
Latino/Admixed American	0.00069	0.00067	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00020	0.00016	rare
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00094	0.00091	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function in the assembly or regulation of proteins in the cornified envelope. The LIM domain may be involved in homotypic or heterotypic associations and may function to localize sciellin to the cornified envelope.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.996
RVIS EVS: 0.11
RVIS percentile EVS: 62.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.485

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High